Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/02—Details
  • A61N1/04—Electrodes
  • A61N1/0404—Electrodes for external use
  • A61N1/0408—Use-related aspects
  • A61N1/0456—Specially adapted for transcutaneous electrical nerve stimulation [TENS]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/36014—External stimulators, e.g. with patch electrodes
  • A61N1/3603—Control systems
  • A61N1/36031—Control systems using physiological parameters for adjustment
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/36036—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation of the outer, middle or inner ear
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/36014—External stimulators, e.g. with patch electrodes
  • A61N1/36021—External stimulators, e.g. with patch electrodes for treatment of pain
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/36014—External stimulators, e.g. with patch electrodes
  • A61N1/36025—External stimulators, e.g. with patch electrodes for treating a mental or cerebral condition

Definitions

• the invention relates to a closed-loop system, device and method for treating the diseases and/or disorders wherein the evoked potential/reflex skin response or any electrical skin recording is measured concurrently with or immediately after the invasive or minimally invasive or noninvasive stimulation of the auricular vagus nerve and the stimulation parameters are automatically adjusted based on this measurement.
• the autonomic nervous system is a system controlling all of the vital functions of the body. In other words, all of the functions of our organs that are not able to be controlled by our are managed by the autonomic nervous system.
• the activity of the autonomic nervous system varies during the daily life, serving to enable our body to accommodate the changes in the internal and external environment.
• the impairments in the variable activity of the autonomic nervous system lead to the impairment in the body's ability to adapt to the variables in the internal and external environment, resulting in the emergence of the autonomic dysfunction and the associated diseases.
• Activation of the nerves via stimulation is employed for the treatment of the resulting disorders and diseases.
• the nerves may be stimulated by sending electrical signals to various nerves from various parts.
• the stimulation is realized via different parts of different nerves by means of the signals of different electrical property for treating different disorders.
• the properties of the stimulation signal to be sent vary according to the disorder intended to be treated, not every stimulation exhibits the same effect in every patient. It is even necessary to differentiate the electric signals to enable stimulation according to the condition of the patient during a particular day, in order to achieve a more effective treatment.
• the nerve to be stimulated and even the stimulation zone of the nerve differs according to the type of the disease intended to be treated. Consequently, the type of the stimulus may also vary.
• the components to provide the stimulation may be positioned under the skin or the stimulation may be performed on the skin, according to the type of the nerve to be stimulated. Although the point at which the stimulation is performed, the position of the stimulator and the electric signals sent for stimulation vary according to the disorder intended to be treated, these do not differ according to the individual or according to the condition of the individual on a particular day and thus, it is not possible to achieve a treatment with desired efficacy.
• US2020179689A1 discloses a system and a method developed for the treatment of migraine attacks.
• the electrodes are attached to the forehead of a patient and the stimulation of the trigeminal nerve is provided via the electric signals for the purpose of treating the migraine attacks.
• the system disclosed in said document is a system designed for the treatment of a specific disorder and sends the electric signals according to the disorder planned to be treated, rather than the individual.
• US2019358452A1 also discloses a system for stimulating the nerves for the treatment of the disorders.
• the stimulation of the nerves is performed noninvasively via the skin of the patient.
• An exemplary embodiment of said system aims at treating the migraine attacks by way of stimulation of the vagus nerve via the patient's neck.
• the data exchange takes place between the stimulator and the station where the stimulator is positioned and even with an interface device. It is possible to save the obtained data in a database, transfer the data via Internet to other devices and present the data to the patient.
• the stimulation parameters may be transferred from the stimulator station to the stimulator via a remote computer under the control of the physician.
• US2015142082 similarly aims at treating a disorder via the electrical stimulation of the nerve.
• the most notable difference of said system from the above-described systems is that it comprises a biological feedback mechanism.
• Said physiological output may be a value such as the pulse variability, electrocardiogram, blood flow and finger temperature. Said values are measured with the help of various sensors and the electrical signals sent for stimulating the nerve are revised in line with the measured values.
• the invention differs from the systems according to the state of the art in that it provides a closed-loop device, system and method for treating migraine, other primary headaches, fibromyalgia, chronic pain, depression, hyperinflammation, autoimmune diseases, cytokine storm, recovery, university performance enhancement, sexual performance enhancement and all the other diseases and/or disorders, especially the diseases resulting from autonomic nervous system dysfunction, wherein the evoked potential/reflex skin response or any electrical skin recording is measured via the ear or via any location where the vagus nerve is present or via the associated nerves concurrently with or immediately after or by allowing some time to elapse after the invasive or minimally invasive or noninvasive stimulation of the auricular vagus nerve and the stimulation parameters are automatically adjusted based on this measurement.
• An object of the invention is to develop a device, a system and a method wherein the treatment of diseases and/or disorders is enabled by the electrical stimulation of the nerves.
• Another object of the invention is to develop a device, a system and a method wherein the treatment of diseases and/or disorders is enabled by the electrical stimulation of the auricular vagus nerve.
• Another object of the invention is to develop a device, a system and a method measuring the evoked potential/reflex skin response or any electrical skin recording concurrently with or immediately after or by allowing some time to elapse after the invasive or minimally invasive or noninvasive stimulation of the vagus nerve and automatically adjusting the stimulation parameters based on this measurement.
• Figure 1 A flow chart of the embodiment according to the invention
• Figure 2 A diagram of the vagus nerve stimulation and evoked potential/reflex skin response or any electrical skin recording measurement biofeedback system
• Figure 3 A graph showing the stimulation and the subsequent measurement of evoked potential/reflex skin response or any electrical skin recording
• Figure 4 A view of the system according to the invention during the use
• Figure 5 A view of the ear electrode
• Figure 6 A view of the stimulator
• Measurement sensor 4 Cable
• the invention relates to a closed-loop device, system and method for treating migraine, other primary headaches, fibromyalgia, chronic pain, depression, hyperinflammation, autoimmune diseases, cytokine storm, recovery, university performance enhancement, sexual performance enhancement and all the other diseases and/or disorders, especially the diseases resulting from autonomic nervous system dysfunction, wherein the evoked potential/reflex skin response or any electrical skin recording is measured via the ear or via any location where the vagus nerve is present or via the associated nerves concurrently with or immediately after or by allowing some time to elapse after the invasive or minimally invasive or noninvasive stimulation of the auricular vagus nerve and the stimulation parameters are automatically adjusted based on this measurement.
• the system is able to stimulate the auricular vagus nerve in the patient's ear via the surface of the ear skin with a mono-phasic, bi-phasic or tri-phasic stimulator (S) or with a plurality of stimulators (S).
• the system is able to apply invasively or minimally invasively or noninvasively to the auricular vagus nerve the electrical, optical, acoustic, magnetic or other types of impulses representing a square, rectangular, triangular, random waveform or a combination of these.
• the system has a measurement sensor (3) available for measuring the evoked potential/reflex skin response or any electrical skin recording while applying the impulses.
• Said measurement sensor (3) may measure invasively or noninvasively or minimally invasively the evoked potential (EP) / reflex skin response (RSR) or any electrical skin recording via the skin surface in the ear.
• the stimulation parameters may be adjusted via the biofeedback system based on the measurement of evoked potential/ reflex skin response (RSR) or any electrical skin recording.
• the evoked potential (EP) / reflex skin response (RSR) may serve many functions including starting the stimulation, stopping the stimulation and customizing the parameters.
• the system includes the neural signal monitoring and/or measurement sensors (3) to enable the post-stimulation measurements of evoked potential (EP) / reflex skin response (RSR) on the stimulated nerves and on the nerves that are not stimulated but may be associated with the stimulated nerves.
• EP evoked potential
• RSR reflex skin response
• the auricular vagus nerve in the right ear is stimulated and then, the EP/RSR measurement is made for the non-stimulated vagus nerve in the left ear either by allowing or not allowing a certain time to elapse after the stimulation.
• the auricular vagus nerve in the left ear is stimulated this time and then, the EP/RSR in the right ear is measured again by allowing or not allowing a certain time to elapse after the stimulation.
• the current parameters are optimized specifically for the individual. How this optimization is performed will be described later in this patent disclosure.
• This is the basic operating mechanism of the system according to the invention. It is this mechanism that distinguishes the present invention from the vagus nerve stimulation mechanisms disclosed in the patents of the state of the art. The reason is that the auricular vagus nerve stimulation is not a novel subject and the most significant drawback in this subject lies in the inability to customize and optimize the stimulation parameters for a particular individual.
• the biofeedback systems available in the literature are directed to monitor various physiological parameters (such as heart rate, heart rate variability and respiration).
• physiological responses are indirect responses and are not sufficient to operate a robust closed-loop biofeedback system.
• physiological responses are influenced by many internal and external factors (such as stress, ambient temperature, fasting, hormonal changes, lack of sleep and exercise), besides the vagus nerve stimulation. Accordingly, they can include the effect of the vagus nerve stimulation only partially.
• evoked potential or any electrical skin responses via the stimulated nerve itself enables more precise data to be obtained about the stimulation by eliminating the internal and external factors.
• the evoked potential/RSR may include many information like whether the nerve in question (here the auricular vagus nerve) has been stimulated, the extent to which it has been stimulated and whether there is placebo effect and is more reliable than the other physiological parameters. This makes the measurement of evoked potential/RSR for the auricular vagus nerve stimulation a genuine invention.
• the EP/RSR measurements serve to start, stop and terminate the stimulation as well as optimize and customize the characteristics of amplitude, frequency, pulse width, mode, waveform, duration and all the other stimulation parameters. In this way, the stimulation parameters are adjusted to particular needs of a patient and the success chance of the treatment is increased, while minimizing the risk for side effects.
• the signal modality burst and/or continuous and/or other
• the electrical and/or optical and/or magnetic and/or acoustic and/or other stimulation and to alter the pulse width, amplitude, inter-phase delay for the mono-, bi- and tri-phasic stimulation, stimulation waveform (square, rectangular, sinusoidal, triangular, random and/or a combination of these), frequency, and stimulation phase (mono-, bi- or triphasic).
• the invention may compare the evoked potentials/RSR measured via vagus nerve and other associated nerves (direct response) with the other physiological responses such as heart rate, heart rate variability, EEG activity and respiration (indirect response). While the system may optimize the stimulation parameters according to evoked potential/electrical skin responses only, it may also include in the evaluation the secondary physiological responses when necessary. It may further improve the optimization of the stimulation parameters by querying the internal and external factors likely to affect the autonomic nervous system activity (such as stress level, ambient temperature, fasting, menstruation, lack of sleep and exercise) in the mobile phone application.
• the autonomic nervous system activity such as stress level, ambient temperature, fasting, menstruation, lack of sleep and exercise
• the invention relates to a closed-loop device, system and method for treating the diseases and/or disorders wherein the evoked potential/RSR is measured via the ear or via any location where the vagus nerve is present or via the associated nerves concurrently with or immediately after or by allowing some time to elapse after the invasive or minimally invasive or noninvasive stimulation of the auricular vagus nerve and the stimulation parameters are automatically adjusted based on this measurement.
• the evoked potential/RSR is measured via the ear or via any location where the vagus nerve is present or via the associated nerves concurrently with or immediately after or by allowing some time to elapse after the invasive or minimally invasive or noninvasive stimulation of the auricular vagus nerve and the stimulation parameters are automatically adjusted based on this measurement.
• the invention relates to a closed-loop device, system and method for treating migraine, other primary headaches, fibromyalgia, chronic pain, depression, hyperinflammation, autoimmune diseases, cytokine storm, recovery, university performance enhancement, sexual performance enhancement and all the other diseases and/or disorders, especially the diseases resulting from autonomic nervous system dysfunction, wherein the evoked potential/RSR is measured concurrently with or immediately after or by allowing some time to elapse after the invasive or minimally invasive or noninvasive stimulation of the auricular vagus nerve and the stimulation parameters are automatically adjusted based on this measurement.
• the present invention comprises the electrical current or voltage stimulations for stimulating, via the user's skin noninvasively or minimally invasively or invasively, the auricular vagus nerve present in the user's ear.
• the stimulations may be acoustic, photonic and/or magnetic for generating a similar effect.
• the electrical stimulation will be described in more detail here.
• the object of the invention is to enable the treatment of any disease by achieving a therapeutic outcome in a user or to maintain the health condition of a user who is currently well.
• the evoked potential/RSR which is the feedback obtained from the nerve as a result of the electric currents applied by the device, and the way how this is performed constitute the subject of the invention.
• the feedback may be obtained via a method including but not limited to evoked potential/RSR; i.e. other methods are also possible.
• the device electrically stimulates the auricular vagus nerve in the ear for various medical purposes.
• the device preferably positioned in the ear or at a point proximate to the ear, measures simultaneously the evoked potential/RSR in a noninvasive manner via the user's ear.
• the measurement may be made via the ear subjected to the stimulation or the other ear not subjected to the stimulation.
• the vagal action potentials emerging after the device electrically stimulates the vagus nerve create the evoked potential/RSR as they propagate through the central nervous system.
• the impact of this evoked potential/RSR is measured by means of at least one measurement sensor (3) available on the device.
• the stimulation with the present invention may be applied also to the other nerves including but not limited to the nerves in the ear and the nerves outside the vagus around the ear (such as trigeminal, facial and glossopharyngeal nerves).
• the artifacts which may affect the evoked potential/RSR may be measured, cleared, and eliminated via the method according to the invention.
• the present invention is based on the principle of automatically adjusting the stimulation parameters by measuring the evoked potential/RSR with a view to achieve optimum customized therapy efficacy and safety after the measurement of the evoked potentials/RSR originating from the stimulation.
• the invention may further evaluate the other physiological responses such as heart rate, heart rate variability, EEG activity and respiratory rate via other sensors and/or wearable devices and/or smart wristbands and the other factors such as stress level, ambient temperature, fasting, menstruation, lack of sleep and exercise via the mobile phone application.
• the evoked potentials/RSR are definitely included in the optimization of the stimulation parameters, while the other data may be used by the system only in cases considered necessary.
• Figure 2 shows a closed-loop system for obtaining the evoked potential/RSR data.
• the device constituting the subject of the invention adjusts the stimulation parameters specific to the individuals, based on the analysis of the evoked potentials/RSR measured via the ear that is subjected to the stimulation or via the other ear.
• the statistical analysis for the stimulation parameters and evoked potential/RSR is employed for selecting the patients as the candidates for therapy and estimating the outcome of the Vagus Nerve Stimulation (VNS) and the possible side effects of the same.
• VNS Vagus Nerve Stimulation
• the wave parameters (e.g. amplitude, frequency, inter-phase delay, wave mode, waveform, etc.) of the nerve stimulator (S) may be automatically altered based on the EP/RSR parameter results obtained by means of the measurement sensor (3) and this loop may be continued until the parameters reach the optimum values by repeating the EP/RSR measurement based on the stimulation performed in the next step.
• the signal modality burst and/or continuous and/or other
• the electrical and/or optical and/or magnetic and/or acoustic and/or other stimulation and to alter the pulse width, amplitude, inter-phase delay for the mono-, bi- and tri-phasic stimulation, stimulation waveform (square, rectangular, sinusoidal, triangular, random and/or a combination of these), frequency, and stimulation phase (mono-, bi- or tri-phasic).
• the purpose for doing so is to collect the EP/RSR data from the individual in order to identify a customized stimulation parameter and protocol, thereby increasing the success chance of the treatment for the individual as well as minimizing the risks for possible side effects.
• this method may also be used for the selection and screening of the potential patients to benefit from said treatment based on the data to be gathered via the EP/RSR measurements.
• Another advantage of the disclosed invention is the ability to enable via the EP/RSR measurements performed the assessment of whether the respective nerve (auricular vagus nerve) has been stimulated, whether the placebo effect exists, whether the stimulated points and hence the positions of the electrodes (2) placed in the ear are correct and whether the stimulation parameters are appropriate.
• the stimulation parameters, stimulation zones and all the other variables may be customized and optimum settings may be identified for a particular individual, owing to the measurements taken.
• the evoked potential/RSR measurement may be used in optimizing the auricular vagus nerve stimulation.
• the system may use the result of this measurement for verifying that the action potential is created in the vagus nerve during and/or following the electrical stimulation. In this way, the system is able to alter the parameters of the electrical stimulation and all the other types of stimulation generated by the vagus nerve stimulator (S) in order to ensure that the auricular vagus nerve stimulation is achieved in a therapeutically effective and safe manner.
• S vagus nerve stimulator
• the system may alter the stimulation parameters such as amplitude, frequency, pulse width, inter-phase delay, waveform, etc.
• an operator may change the layout or orientation of the electrodes (2) or the device on the skin position of the patient in order to enable the vagus nerve to be stimulated properly.
• the system includes the components like software, firmware and hardware in order to update and fix the parameters of the stimulation.
• the system software, firmware and hardware components fix the stimulation signal based on the measured physiological parameters (evoked potential/RSR).
• the signal generator will apply a fixed electrical impulse to the patient.
• a doctor may manually optimize the stimulation in the hospital environment or perform the optimization online in an outside environment by applying the electrical stimulation and measuring the effects of the same on the body parameters.
• the optimization of stimulation may be performed autonomously by the device and the system itself.
• the optimization and customization of the stimulation parameters are performed automatically by the device and the system.
• the patent application US20100004705 and US20100003656 by KILGARD for the treatment of tinnitus apparently also uses the term biofeedback in the manner intended.
• the application discloses the concurrent use of the electrical neural stimulation, including the use of invasive vagus nerve stimulation, with the biofeedback therapy (besides the other therapies).
• the relationship disclosed between the biofeedback therapy and the neural stimulation relates only to the mutual timing of these.
• the embodiments do not include any information to suggest that the actual parameters of the nerve stimulation will be modulated along with the power of the biofeedback signal itself or the power of the physiological signal serving as the basis for the biofeedback signal.
• the electrical stimulation and the biofeedback signals are described as separate entities in this patent application.
• the electrical stimulation is shown as an invasive procedure in the figures and the biofeedback is generally understood as a noninvasive procedure.
• the electrical stimulation itself may contain a feedback signal and both the electrical nerve stimulation and the feedback methods are the noninvasive procedures.
• the electrical stimulation is said to induce plasticity in the brain via the basal nuclei, locus coeruleus or amygdala activation for instance, thereby increasing the efficacy of the biofeedback therapy.
• the present invention does not necessarily include neuronal plasticity and the present invention is further capable of enabling the stimulation of the basal nuclei, locus coeruleus, amygdala and many other brain components without inducing the plasticity.
• the present invention differs from the prior art relating to the vagus nerve stimulation and biofeedback.
• the reason is that the present invention involves the differences such as the use of evoked potential (EP) /RSR measurements as the feedback method, these measurements being, unlike the other inventions, taken from the ear, these measurements being, again unlike the other inventions, obtained after the stimulation and being taken preferably from the other ear not subjected to stimulation rather than the ear where the stimulation is performed ( Figures 2 and 3), the resulting minimization of the artifacts and the possibility to allow precise measurement of the activation potential on the nerve, and further, the real-time adjustment of the stimulation, measurement and optimization.
• EP evoked potential
• RSR evoked potential
• the present invention stimulates the auricular branch of the vagus nerve.
• the application of the present invention involves the transmission of all kinds of stimulation/s including the electrical stimulation in particular, for the purpose of treating the medical conditions and preserving the healthy condition of a user.
• the device comprises at least one signal generator generating the signal to be sent from the electrodes (2), a power supply connected to the generator, a control unit connected to the former two, the electrodes (2) enabling to transmit the signal to the nerve via the skin by means of cables, and a measurement sensor (3).
• a compact design may be employed for the subcomponents of the device and the method and the device may allow a user to alter the parameter settings for therapeutic stimulation applications.
• the device comprises a total of two measurement sensors (3), one in each ear.
• the ear electrodes (2) are present in a total quantity of 4, two in each ear.
• the stimulation will be performed via one ear while the measurement will be performed via the other ear with the help of the measurement sensor (3), and after the measurement via the other ear, the stimulation will be performed this time via the ear previously subjected to measurement and accordingly, the measurement will be performed this time via the ear initially subjected to stimulation.
• the application is not limited to the above and the measurement may be taken also from the ears subjected to stimulation.
• the elastic piece (1) which enables the device to remain fixed in the user's ear, extends around the earlap to enable the electrodes (2) to remain stable.
• the ear electrodes (2) shown in Figure 5 are designed to contact the tragus and concha parts of the ear. It is thus aimed to stimulate maximum vagus area by increasing the distance between the electrodes (2).
• the electrodes in each ear is arranged such that one is (-) and the other is (+).
• the sensor (3) to measure the evoked potential/RSR is positioned between the electrodes. In this way, the sensor (3) is able to contact the area of the ear where the vagus nerve is present. While the sensor (3) is not in contact with the skin when the device is in the off state, it is able to contact the skin by extending between the electrodes (2) by means of a spring system when the device is turned on.
• the electrode (2) required to perform the stimulation has a surface area that contacts the skin surface or beneath the skin surface and has a transmission energy field for an effective treatment within the safety limits according to the current intensity.
• the electrical connection of the stimulator (S) ( Figure 6) with the patient may be ohmic or capacitive.
• the cable output portion (63) where said cable output (5) is present has a relatively elastic structure.
• the body end portion (61) and the body middle portion (62) containing the stimulator (S) parts like battery and electronic card are manufactured from a more rigid plastic material.
• At least one control member (7), more specifically at least one on/off button, is present on the stimulator (S).
• At least one visual warning member (8) indicating the status of the device is present on the stimulator (S).
• the parts of the device such as battery and electronic card are positioned in the body middle portion (62).
• the control unit controls the impulse generator for generating a signal for each of the electrodes (2) or transducers of the device.
• the control unit may comprise a general-purpose computer including one or more MCU, computer memories for storing the executable computer programs (including the system's operating system), computer memories for storing and retrieving data, disk storage devices, communication devices (like serial and USB connection ports) for a patient or clinician for accepting the external signals from the system keyboard, computer mouse and touch screen as well as the externally provided signals, monitor units and/or light indicators, analog-digital convertors for digitizing the analog signals like analog evoked potentials and/or physiological signals, communication devices for data transmission and receipt to and from the external devices like printers and modems forming part of the system, information about the monitors forming part of the hardware system to provide the display, buses to interconnect the above- mentioned components, and human interfaces for such an operator.
• the user may operate the system and display the results in a device by typing instructions for the control unit via a device like keyboard and/or via input devices such as buttons with mechanical movement or resistive buttons or capacitive touch buttons with sensor.
• the system may direct results to the computer monitor or to a printer, modem and/or storage disk or to display units on the controller or at another location and/or may comprise the indicator lights and/or audio signals including recorded or synthesized speech.
• the control of the system may be manual or may be based on the feedback measured from the evoked potentials/RSR.
• the parameters for the nerve and tissue stimulation consist of the following: Current and/or voltage amplitude, frequency, pulse width, inter-phase delay, pulse train duration (or number of pulses), wave modality (mono-, bi-, tri-phasic), wave form (sinusoidal, square, rectangular, triangular or a mixture of these).
• the electrodes (2) of the invention are used to deliver the stimulation to the ear surface noninvasively, minimally invasively or invasively.
• the electronic components generating the signals applied to the electrodes (2) may be separate components.
• the connection to the generator may be achieved by the use of cables and the wireless connection is also possible.
• the system may comprise a multiplicity of generators.
• the mechanical and electronic components (impulse generator, control unit and power supply) of the stimulator (S) are compact and portable; however, they can also be fixed and/or a part of the existing equipment.
• One of the novelties of such an invention is that it shapes the stimulation parameters along with the measurement as a result of the stimulator (S) generating a selective physiological response by stimulating the nerve, but it avoids overstimulation or understimulation of the nerves and tissue outside the targeted therapy. In this way, a possible side effect is avoided and the success chance of treatment increases.
• control unit and/or power unit of the nerve stimulator (S) may remain physically separate from the housing of the stimulator (S) in order to provide convenience for the user, and in case it is separate, the separate parts of the system may establish communication with one another.
• the use of wireless communication may assist in keeping the control procedures away from a sterile area in the operating room.
• the communication between the devices preferably utilizes Bluetooth communication.
• a near field communication method maybe employed, whereby a simplex or full- or half-duplex communication channel may be formed through the use of a magnetically connected communication path.
• any ISM frequency band may still be used in the manner described above.
• the use of far field or near field or both near field and far field communication may be present in the same embodiment. One or simultaneously both of these may be employed depending on the selected frequency operation, for various applications such as controlling the system while simultaneously receiving the operational data (e.g. stimulation parameters, evoked potential parameters, etc.).
• 2,4 GHz-based transceivers offer high data rates (over 1 Mbps) and a smaller antenna as compared to those operating at lower frequencies, which features make them more suitable for the short range devices.
• 2,4 GHz wireless standard Wi-Fi and ZigBee
• ZigBee wireless standard operates at 2,4 GHz in most domains around the world, it also operates at the frequencies of 868 MHz ISM in Europe and 915 MHz ISM in USA and Australia.
• the data transfer rates vary in the range of 20 to 250 kilobytes/second with this standard.
• ZigBee Alliance 2400 Camino Ramon Suite 375 San Ramon, California 94583 The systems for connecting the smart phones with the physiological sensors by the use of Bluetooth may also be employed.
• BioZen which is designed specifically for the biofeedback applications, is based on the open-source Bluetooth Sensor Processing framework for Android smart phones and may be provided free of charge. It may connect wirelessly with many commercially available physiological sensors [Anonymous. BIOZEN User Manual, United States Department of Defense National Center for Telehealth and Technology. 9933 West Hayes Street, Joint Base Lewis-McChord, Wash. 98431, page 1-16, 2013],
• measurement of an evoked potential/RSR may be employed for optimizing the vagus nerve stimulation. Considering that a certain evoked potential/RSR representing the vagus nerve stimulation may be measured, the operator may use this measurement to verify that the action potentials are created in the vagus nerve during the electrical stimulation.
• the system may automatically alter the parameters for the electrical impulses generated by the vagus nerve stimulator (S), in order to ensure that such stimulation evokes the vagus nerve in a therapeutically effective manner.
• S vagus nerve stimulator
• Certain structures of the central nervous system or other physiological systems affected by the vagus nerve stimulation are dependent upon the parameters of the vagus nerve stimulation selected to stimulate a particular system.
• the direct electrical stimulation of the vagus nerve will create evoked potentials/RSR as the resulting vagal action potentials and their sequels propagate through the central nervous system.
• Figure 2 shows a closed-loop (feedback) system for setting the parameters for the stimulus or stimuli via the data obtained from the measurement of evoked potential/RSR.
• the vagus nerve stimulator (S) may alter in real-time a parameter (e.g. amplitude or frequency) of the nerve stimulus waveform as a result of the measured EP/RSR parameters.
• the vagus nerve stimulation parameters may be altered automatically and in real-time depending on the values from the measurements of evoked potentials/RSR, by means of the methods of the control theory.
• An accelerometer or a plurality of accelerometers may be used to detect the movement and the stopping.
• the combined accelerometer outputs at the position of each accelerometer make it possible to measure any movement of the stimulator (S) relative to the underlying skin.
• the optimal choice of the parameters for the feedback controller may be via a calculation based on the correlation between the stimulator (S) parameters and the measured evoked potentials. Therefore, the choice of the controller parameters (setting) is realized through the tests where a calculated error value is used for constituting the system input for the closed-loop installation.
• the control unit may also employ the feedforward methods [Coleman BROSILOW, Babu Joseph. Feedforward Control (Chapter 9), In: Techniques of Model-Based Control. Upper Saddle River, NJ: Prentice Hall PTR, 2002. pp, 221-240],
• the controller may be a type of predictive controller.
• a mathematical model of the system is needed to realize the predictions of the system behavior for the purpose of including the predictions in a feedforward control device. If the mechanisms of the systems are not understood by an extent sufficient to form a model with physiological basis, a black box model may be used instead.
• Such models include autoregressive models [Tim BOLLERSLEV. Generalized autoregressive conditional heteroskedasticity. Journal of Econometrics 31 (1986): 307-327], [James H. STOCK, Mark W. Watson. Forecasting with Many Predictors, In: Handbook of Economic Forecasting. Volume 1, G. Elliott, C. W. J. Granger and A. Timmermann, eds (2006) Amsterdam: Elsevier B.
• Kalman filters [Eric A. WAN and Rudolph van der Merwe. The unscented Kalman filter for nonlinear estimation, In: Proceedings of Symposium 2000 on Adaptive Systems for Signal Processing, Communication and Control (AS-SPCC), IEEE, Lake Louise, Alberta, Canada, October, 2000, pp 153-158], wavelet transforms [O. RENAUD, J. -L. Stark, F. Murtagh. Waveletbased forecasting of short and long memory time series. Signal Processing 48 (1996): 51-65], hidden Markov models [Sam ROWEIS and Zoubin Ghahramani. A Unifying Review of Linear Gaussian Models.
• Neural Computation 11 (2, 1999): 305-345]
• artificial neural networks [Guoquiang ZHANG, B. Eddy Patuwo, Michael Y. Hu. Forecasting with artificial neural networks: the state of the art. International Journal of Forecasting 14 (1998): 35-62],
• a stimulator (S) parameters training set including whether a variable is outside the desired range, will be obtained and this will be associated with an evoked potential/RSR measured.
• the electrical stimulation of the vagus nerve and/or skin secondarily causes the stimulation of the brain regions involved in sensory processing, autonomic nervous system regulation and conscious action.
• the selection of the stimulation waveform parameters may be performed experimentally for preferentially modulating certain regions of the brain wherein a series of electrical stimulation waveform parameters (amplitude, frequency, pulse width, etc.) are selected.
• the responsive region of the brain may be measured using fMRI or a related imaging method [CHAE J H, Nahas Z, Lomarev M, Denslow S, Lorberbaum J P, Bohning D E, George M S. A review of functional neuroimaging studies of vagus nerve stimulation (VNS). J PsychiatrRes.
• a database may be formed such that the inverse problem of selecting the parameters that will fit a certain selected brain region and the corresponding evoked potentials may be solved by consulting the database.
• the automated adjustment of the stimulation parameters and their association with the evoked potentials/RSR target optimum customized treatment for the patients and users.
• An object of the disclosed stimulator (S) is to provide both nerve fiber selectivity and positional selectivity.
• the positional selectivity may be obtained partially through the design of the electrode (2) configuration and the nerve fiber selectivity may be obtained partially through the design of the stimulator (S) waveform; however, the designs for the two selectivity types are interwoven.
• the reason is that a waveform for instance selectively stimulates only one of two nerves, irrespective of whether they are proximate to each other, thereby eliminating the need for focusing the stimulator (S) signal on only one of the nerves [GRILL W and Mortimer J T. Stimulus waveforms for selective neural stimulation. IEEE Eng. Med. Biol. 14 (1995): 375- 385],
• the invasive nerve stimulation typically uses square wave pulse signals.
• the square waveforms are not ideal for the noninvasive stimulation of the vagus nerve as they cause excessive pain.
• Prepulses and similar waveform modifications have been suggested as methods for improving the selectivity of the nerve stimulation waveforms [Aleksandra VUCKOVIC, Marco Tosato and Johannes J Struijk. A comparative study of three techniques for diameter selective fiber activation in the vagal nerve: anodal block, depolarizing prepulses and slowly rising pulses. J. Neural Eng. 5 (2008): 275-286; Aleksandra VUCKOVIC, Nico J. M. Rijkhoff, and Johannes J. Struijk.
• the vagus nerve includes the fibers (afferent) transmitting the sensory information about the condition of the body organs back to the central nervous system, in addition to the efferent output fibers transmitting signals from the central nervous system to various organs of the body.
• Different treatment protocols may be employed depending on the medical indication, whether the treatment is chronic or acute, and the natural history of disease.
• the vagus nerve stimulation may have stimulating and inhibiting effects.
• the present invention uses the two- way connections of the solitary tract nucleus (NTS) with the structures producing inhibitory neurotransmitters or utilizes the connections of NTS with hypothalamus reflecting the structures producing inhibitory neurotransmitters. Similar effects are combined within NTS itself and the combined inhibitory effects on NTS and dorsal motor nucleus generate an overall inhibitory effect.
• NTS solitary tract nucleus
• the sensory stimuli are applied to evoke the potentials corresponding to external sense organs.
• the vagus nerve stimulation was used also in other interventions in order to measure the evoked potentials with the electrodes (2) in the head.
• the potentials suggested in the oldest studies to be evoked via invasive vagus nerve stimulation were determined to be the artifacts including the muscle stimulation generated in the region of the stimulating electrodes (2) located in the neck region [HAMMOND E J, Uthman B M, Reid S A, Wilder B J. Electrophysiologic studies of cervical vagus nerve stimulation in humans: II. Evoked potentials. Epilepsia 33 (6, 1992): 1021-1028],
• an operator or an automated feedback loop system may use this measurement for verifying the generation of the action potentials in the vagus nerve during or after the electrical stimulation.
• an operator or an automated system may alter a characteristic of the electrical impulse generator via the vagus nerve stimulator (S) in order to ensure that such stimulation stimulates the vagus nerve in a therapeutically effective manner.
• S vagus nerve stimulator
• an operator or an automated system may alter the amplitude, frequency, pulse width and/or inter-phase delay of the signal until such evoked potential/RSR is generated.
• Devices and methods according to the present invention may include the combined feedback and automated control mechanisms that begin with the measurement of the evoked potential/RSR characteristics of an individual by the use of measurement sensors (3) in response to the varying parameters of a stimulus.
• a physiological characteristic is the evoked potential/RSR measured using the ear electrodes (2).
• the present invention further devises the measurement and processing of many different signals like heart rate, blood pressure, stopping and movement according to various stimuli or stimuli parameters.
• EEG electromyogram
• the methods for treating a patient according to the present invention comprise the stimulation of the vagus nerve by the use of electrical stimulation devices and stimulation waveforms.
• the stimulation may be performed on the left or right auricular vagus nerve, or on both nerves concurrently or alternately, while measuring the evoked potentials/RSR via one auricular vagus nerve in the stimulated side or non-stimulated side or in both sides.
• the position and angular orientation of the device are adjusted at the preferred position on the vagus nerve in the ear until the patient perceives the stimulation when the current passes through the electrodes (2).
• the applied current is increased up to a predetermined limit of the stimulation parameters gradually and automatically and by measuring the evoked potential/RSR. This is followed by a stimulation-free period (interim stimulation period).
• a stimulation model that follows a stimulation-free interim stimulation period repeats itself with a T period.
• the preferred form of each pulse may be a square, rectangular, sinusoidal or triangular or another random waveform.
• FIG. 2 is a more detailed diagram of the nerve modulation device for transmitting the electrical stimulation to the nerves.
• the device comprises an electrical impulse generator, a power supply connected to the electrical impulse generator, a control unit in communication with the electrical impulse generator and connected to the power supply, and one or more stimulation and measurement electrodes (2) connected to the electrical impulse generator.
• the nerve modulation device is configured such that it generates the electrical impulses sufficient to modulate the activity of one or more selected regions of a nerve.
• the control unit may control the electrical impulse generator so that a signal appropriate for improving the condition of the patient may be generated when the signal is applied via the electrodes (2) to the nerve.
• An embodiment of the nerve stimulation device with relatively low power consumption may obtain power from a correspondingly weak and/or remote external transmitter. This may be achieved by designing the device in such a way that it generates a fixed voltage or fixed current.
• the stimulator (S) circuit includes a storage device like a battery or a capacitor for storing power or charge and subsequently delivering the same to the circuit so that the circuit may generate the electrical impulses and transmit these impulses to the electrodes (2).
• the power for the storage device may be wirelessly transmitted to the stimulator (S) circuit via a carrier signal coming from the external controller.
• the electrode (2) and the signal generator are designed essentially for the stimulation of the auricular vagus nerve in the ear, though not being limited to the same.
• the treatment method according to the present invention for treating diseases and/or disorders and/or further improving the current condition of a user without any disease and/or enabling a user in good health to keep their current condition comprises the process steps of
• the method according to the invention comprises the process steps of
• At least one or more than one electrode (2) transmitting an electrical and/or optical and/or magnetic and/or acoustic and/or other stimulation from the system to the nerve, is positioned in contact with the auricular vagus nerve, noninvasively on the outer skin surface or minimally invasively or invasively under the skin surface.
• At least one or more than one electrode (2), transmitting the stimulation to the nerve is positioned noninvasively on the outer skin surface or minimally invasively or invasively under the skin surface and the voltage fluctuation originating from an ionic current inside the brain or another part of the nervous system is measured.
• the acute response or chronic response is measured and assessed as an indicator of the medical condition of the user following an electrical and/or optical and/or magnetic and/or acoustic and/or other stimulation. It is possible to alleviate a medical disorder including but not limited to pain as the acute response or the chronic response.
• the evoked potential/RSR measurement would be able to be used during or after the stimulation for verifying the generation of the action potentials in the vagus nerve and/or another nerve or for detecting whether the action potentials have formed or whether the action potentials have changed.
• the action potential in the auricular vagus nerve and/or another nerve to be an increase in the habituation of the evoked potential (EP) /RSR or a decrease in the habituation of the evoked potential (EP) /RSR.
• An electrical and/or optical and/or magnetic and/or acoustic and/or other stimulation may alter the action potential in the auricular vagus nerve. It is possible for the action potential in the auricular vagus nerve and/or another nerve to be related to an increase in the habituation of the acute response to the electric potential or a decrease in the habituation of the acute response to the electric potential or, it is possible for the action potential in the auricular vagus nerve and/or another nerve to be related to an increase in the habituation of the chronic response to the electric potential or a decrease in the habituation of the chronic response to the electric potential.
• the pulse instruction may have an address or other associated identifier and thus, only a certain signal generator may be activated. This will allow having more than one signal generator, each responding to its own instruction coming from the same or more than one power/control unit, on a patient's body.
• Another option may be having a circuit or processor in an implanted signal generator, said circuit or processor being capable of transmitting a signal to the power/control unit.
• This signal may contain the status information like voltage, current, number of pulses applied or other applicable data.
• the antennas and RF signals in this system may be replaced by closely connected wire coils and inductively connected signals of lower frequency.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Biomedical Technology (AREA)
• Engineering & Computer Science (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Radiology & Medical Imaging (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Biophysics (AREA)
• Otolaryngology (AREA)
• Physiology (AREA)
• Heart & Thoracic Surgery (AREA)
• Electrotherapy Devices (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=82260974

Family Applications (1)

Country Status (2)

Citations (3)

• 2020
  • 2020-12-30 TR TR2020/22383A patent/TR202022383A1/tr unknown
• 2021
  • 2021-06-14 WO PCT/TR2021/050577 patent/WO2022146295A1/en active Application Filing

Patent Citations (3)

Also Published As

Similar Documents

Legal Events